I was watching Fox 5 NY when they began talking about a girl with DMD. The report then went into how a family (didn't recognize their name) was trying to get an experimental drug approved asap. The father said the drug was reversing the effects of this disease. The reporter then said the drug was......ETEPLIRSEN and then said they were looking for approval from the FDA in February. Unfortunately i don't think they mentioned Sarepta but i was excited!
I searched the FOX NY website and found an article on a 3 year old boy with DMD. The childs name is Pietro Scarso . His parents want Etiplersen to be given fast track approval so their child has a chance at a normal life. He is not currently in the study. Yahoo won't let me post a link, but anyone searching can find the article.
Conventional medical wisdom has it that females don't get Duchenne muscular dystrophy (DMD) or most other "X-linked" disorders -- disorders that arise from flaws, or mutations, on X-chromosome genes.
The reasoning is sound: A female has two X chromosomes to a male's one, so she has a built-in "backup" if anything should go wrong on either of her two Xs. She can be a "carrier" of an X-linked disease, because she can give a flawed X chromosome to her sons, who, having only one X, will likely develop an X-linked disorder.
DMD is one of many X-linked diseases, such as two kinds of hemophilia (including one that affected generations of European royalty) and red-green color blindness.
The gene for a muscle protein known as dystrophin is located on the X chromosome, and mutations in it were identified as the cause of DMD by MDA researchers in 1986. In boys with DMD, the lone X chromosome has only one dystrophin gene; if there's a mutation in that gene, the boys' muscles will lack dystrophin and slowly degenerate. Skeletal muscles and heart muscles are affected.
A girl almost always has two dystrophin genes and, even if one of them isn't working, the other should suffice to keep dystrophin levels high enough to preserve muscle function in both the heart and skeletal muscles. Should and usually does. But research has shown that a small minority of females who have both a working and a nonworking dystrophin gene do show symptoms of DMD.
Erin Cutinella of Bandon, Ore., is what's known as a DMD "manifesting carrier" -- a female carrier of a DMD gene mutation who also has symptoms of DMD herself. (One could say, with some justification, that manifesting carriers actually have DMD, although usually in a mild form.) Although their disorder varies in severity, all manifesting carriers of DMD have one thing in common -- not enough dystrophin.
Cutinella's condition was diagnosed in childhood, when she showed enlarged calf muscles (a sign of muscular dystrophy) and couldn't run. Her doctor told her that any male children she had stood a 50-50 chance of having DMD. "Some have taken that chance and gotten lucky," she says; but luck wasn't with her. Her only son was born with DMD (he would later die in an auto accident), and her own symptoms worsened over the years. She was able to work in the computer field until 1989. In 1991, she left work entirely and started drawing disability benefits.
Now 38, Cutinella finds going up stairs is increasingly difficult and that she can generally do "less and less." She can no longer wash her car or clean her house, and her back hurts constantly from muscle weakness. Frequent falls have resulted in back and knee surgeries, and she can no longer get up after a fall. "I have to crawl," she says. "I'm getting slowly worse, but the doctors don't know what to tell me."
WHEN BACKUP SYSTEMS FAIL
illustration Click for enlarged illustrations.
Like most manifesting carriers, Cutinella doesn't know the reason for her dystrophin deficiency, and it probably wouldn't help her a great deal to know.
But molecular geneticist and MDA research grantee Eric Hoffman is interested in knowing. Hoffman, who recently left the University of Pittsburgh for Children's National Medical Center in Washington, D.C., has been studying DMD carriers and their families.
In very rare instances, a girl may lack a second X chromosome entirely; or, her "backup" X chromosome may be damaged during development. In these cases, a girl can develop many X-linked disorders, including DMD.
There's another way for a girl to develop symptoms of DMD and, in Hoffman's view, it's by far the most common reason for the disorder in girls. The mechanism is a genetic phenomenon known as "skewed X inactivation." In this condition, a girl has the DMD gene mutation on only one of her X chromosomes -- the usual carrier situation. But then her developing body does something unfortunate: Its cells start to rely on the X chromosome with the flawed gene much more often than they do the one with the working gene. The result is that most of her cells show the effects of the gene mutation -- a lack of dystrophin.
"Every cell can only have one X chromosome that's working," Hoffman says. (In contrast, cells have two working copies of all the other chromosomes except the Y.) "If two are working, then the cell will die. Men only have one X, but women have two, so they have to shut down one or the other X chromosome in each cell. That's called X inactivation, and it happens when the human embryo is about 100 cells big."
At the 100-cell stage, Hoffman says, "each cell 'decides' to turn off one X chromosome or the other." That usually works fine, Hoffman says, because the choice is by random chance, and the selection of each X is about 50-50. Even if there's a mutation on one X, 50 percent of cells will use the other X, and that's usually enough to protect a girl from an X-linked disorder.
But when embryonic cells "decide" to use the X chromosome with the mutated gene far more often than 50 percent of the time -- that's when a girl can get DMD or other X-linked disorders.
In DMD carriers with heart problems, it's likely that fewer than half the heart's cells are making dystrophin, and symptoms can result. In skeletal muscle, explains Hoffman, the situation is a little more complicated -- but, happily, a little better, too.
Skeletal muscle cells are made of what were once many smaller cells that fused during fetal development to form one long muscle "fiber" (the name for a mature muscle cell). The boundaries between the individual cells disappear before birth, but the nucleus of each original cell remains in the long fiber. Each nucleus, which once belonged to a separate cell, has made its own "choice" about which X chromosome to use, so, inside each muscle fiber of a DMD carrier there are some nuclei that make dystrophin and others that don't (see illustration).
As in the heart, a 50-50 split of dystrophin-positive and dystrophin-negative nuclei is probably fine for keeping skeletal muscles healthy. But when X inactivation is "skewed" so that too many dystrophin-negative nuclei populate a muscle fiber, dystrophin levels can fall too low for adequate function and the fiber can start to degenerate.